Psoriasis is a chronic, incurable, inflammatory skin condition affecting two to four percent of the world's population. Severity ranges from minor to life-threatening, and often fluctuates. Pathogenesis is unknown, but involves hereditary abnormalities of the immune system, with lymphocyte and neutrophil-mediated inflammation combined with hyperplasia of the epidermis. The epidermis proliferates at about ten times the normal rate. People with psoriasis literally leave a trail of skin flakes, and suffer from chronic itchy lesions, poor temperature regulation, fatigue from constant protein loss, and social stigma to the point of reclusion. There is an associated arthritis which attacks the fingers. The most common form is plaque-type psoriasis, in which well-demarcated lesions appear on the body, with normal skin between them. The plaques are red and scaly, quite different from the surrounding normal skin. The number of plaques ranges from several to several hundred, scattered over the trunk, arms, and legs. Psoriasis tends to spare the face, because ultraviolet (UV) light is therapeutic.
There is no cure for psoriasis. Drug treatments work by anti-inflammatory, antimitotic, hormonal, or immunosuppressive mechanisms. These include topical administration of corticosteroids, tar preparations, and vitamin D3 derivatives, systemic chemotherapy with methotrexate, and immunosuppression with cyclosporin A. Topical treatments are messy and expensive, but are still the main approach for patients with small areas of involvement. Corticosteroids tend to produce partial clearing followed by a “rebound” worse than the original disease severity, cause skin atrophy, and become progressively ineffective over time. Methotrexate is effective but causes liver toxicity. Cyclosporin A has multiple side effects, is expensive, and reserved for severe cases.
Ultraviolet phototherapy with or without photosensitizers, has been a mainstay of psoriasis treatment for many decades. UVB (290–320 nm) phototherapy is practical, effective, and often produces a long remission time after clearing, typically about five months. Psoralen, an extremely potent DNA-crosslinking photosensitizer, is also used orally or topically, followed by exposure to UVA radiation (320–400 nm). This is called Psoralen UVA (PUVA), a type of photochemotherapy. Phototherapy clears plaques in about 90% of patients, by combined mechanisms including apoptosis of keratinocytes, antimetabolic effects of DNA damage, and local and systemic immunosuppression. The patient stands in a “light box” lined with fluorescent lamps or other UV sources, and receives a prescribed fluence, i.e., a therapeutic dose of radiation. Each box is the size of a phone booth and costs about twenty to thirty thousand dollars. Since psoriasis does not usually affect the face, the patient typically wears a mask covering the face and eyes to prevent exposure to the therapeutic radiation. The rate of clearing is variable between patients, and depends on the exposure dose per treatment. An average of 20 to 30 treatments is needed for UVB (given 3 times per week) and an average of 15 to 25 treatments is needed for PUVA (given 2 times per week), depending on aggressiveness of the exposure dose protocol. Hence, it takes several months and many trips to the phototherapy center to clear psoriasis.
The “art” of phototherapy lies in achieving clearing without causing painful sunburn-like reactions. Thus, skin unaffected with psoriasis, i.e., normal skin, limits the therapeutic dose. The minimal erythema dose (MED) in normal skin is defined as the lowest fluence eliciting an inflammatory response, and is used to guide dosimetry. If the patient receives more than 1 MED, a “sunburn” will occur. At 3 MED a painful sunburn with blistering can occur, and at 10 MED a life-threatening burn results. Prior to a phototherapy treatment, the doctor determines the MED for a particular patient. As tanning develops during the course of multiple treatments, the UV fluence is increased, typically by 30 to 50 percent per treatment. At present, phototherapy consists of carefully but aggressively “pushing” the exposure dose based on response of the unaffected skin between plaques of psoriasis.
The cost of phototherapy, based on the number of trips and the clinicians' time, is estimated to be almost 1 billion dollars per year in the US. This does not include the cost of treating of skin cancers induced by phototherapy. In particular, prolonged exposure to UVE and PUVA cause basal cell carcinoma, squamous cell carcinoma, and melanoma. These diseases typically occur in areas of skin between plaques of psoriasis that have been exposed to large cumulative doses of UV radiation during phototherapy.